The objective of the proposed research program is to seek unique plaque microbe associations with clinical measures of early periodontitis in man. The study will employ two subject populations. The first population will contain at least 400 subjects 20-40 years of age. This population will be utilized in a cross-sectional study. The second population will contain about 25 subjects under periodontal treatment and will be studied longitudinally. Data collected for each subject will include comprehensive clinical measurements of disease and comprehensive microbial compositions of appropriate plaque samples. Demographic data and dental/medical histories will also be obtained from each subject. Data obtained from the cross-sectional population will be analyzed by least squares multiple regression methods to seek associations between disease measures individually and collectively and individual, and groups of, microorganisms. Thus, specific microbial etiologies of early periodontitis will be sought. Data from the longitudinal population accumulated over 4 years will be similarly processed to test for associations between specific bacteria and disease recurrence. The results of this comprehensive integrated research program involving clinicians, microbiologists, statisticians, and over 400 subjects will advance our understanding of the etiology of human periodontitis and aid the development of new rational treatment and preventive regimens.